Genetic Variant NM_002479.6:c.105C>T (chr1-203085857-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002479.6(MYOG):c.105C>T(p.Tyr35Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,613,990 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 36 hom. )

Consequence

MYOG
NM_002479.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.56

Publications

2 publications found

Variant links:

Genes affected

MYOG (HGNC:7612): (myogenin) Myogenin is a muscle-specific transcription factor that can induce myogenesis in a variety of cell types in tissue culture. It is a member of a large family of proteins related by sequence homology, the helix-loop-helix (HLH) proteins. It is essential for the development of functional skeletal muscle. [provided by RefSeq, Jul 2008]

MYOG links:

MYOPARR (HGNC:54178): (myogenin promoter associated myogenic regulatory antisense long non coding RNA) Predicted to enable RNA polymerase II core promoter sequence-specific DNA binding activity. Predicted to be involved in myoblast fate specification. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to act upstream of or within protein-containing complex assembly and skeletal muscle fiber development. [provided by Alliance of Genome Resources, Apr 2022]

MYOPARR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-203085857-G-A is Benign according to our data. Variant chr1-203085857-G-A is described in ClinVar as Benign. ClinVar VariationId is 773418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.56 with no splicing effect.

BS2

High AC in GnomAd4 at 483 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002479.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOG	NM_002479.6	MANE Select	c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 3	NP_002470.2
	MYOPARR	NR_160550.1		n.388-626G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOG	ENST00000241651.5	TSL:1 MANE Select	c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 3	ENSP00000241651.4	P15173
MYOG	ENST00000944760.1		c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 3	ENSP00000614819.1
MYOG	ENST00000944761.1		c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 3	ENSP00000614820.1

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

483

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00851

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00338

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00349

AC:

876

AN:

250798

AF XY:

0.00412

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00407

AC:

5947

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3101

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33468

American (AMR)

AF:

0.00119

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26110

East Asian (EAS)

AF:

0.00564

AC:

224

AN:

39698

South Asian (SAS)

AF:

0.0133

AC:

1143

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00375

AC:

4166

AN:

1111954

Other (OTH)

AF:

0.00525

AC:

317

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

339

677

1016

1354

1693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00317

AC:

483

AN:

152238

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41540

American (AMR)

AF:

0.00425

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00853

AC:

AN:

5158

South Asian (SAS)

AF:

0.0160

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00338

AC:

230

AN:

67998

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00304

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00320

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

(source)

DANN

Benign

0.81

PhyloP100

-2.6

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over